Cosyntropin (Cortrosyn / Synacthen)

Prescription

Cosyntropin (also called tetracosactide or tetracosactrin; brand names Cortrosyn and Synacthen) is a synthetic peptide comprising the first 24 amino acids of adrenocorticotropic hormone (ACTH). Natural ACTH is a 39-amino-acid pituitary hormone, but its biological activity — stimulating the adrenal cortex to make cortisol — resides in the first 24 residues. By using only that active fragment, cosyntropin retains full potency while being less likely to provoke immune reactions than animal-derived full-length ACTH. Its principal role is diagnostic. In the ACTH (cosyntropin) stimulation test, a baseline blood cortisol is drawn, a standard dose of cosyntropin is injected, and cortisol is measured again 30 and/or 60 minutes later. Healthy adrenal glands respond by raising cortisol above a threshold; a blunted response suggests adrenal insufficiency. The test helps distinguish primary adrenal insufficiency (Addison's disease, where the adrenals themselves fail) from other causes and is one of the most common endocrine dynamic tests performed. Mechanistically, cosyntropin binds the melanocortin-2 receptor (MC2R) on adrenocortical cells, activating the signaling cascade that drives synthesis and release of cortisol (and, to a lesser degree, adrenal androgens and aldosterone precursors). Because the adrenal response to a single dose is rapid, the test can be completed within an hour. Beyond diagnosis, longer-acting depot forms of tetracosactide have been used therapeutically in some countries for conditions where ACTH-driven effects are desired (for example certain inflammatory or seizure disorders), though this is region- and indication-specific. Cosyntropin is generally well tolerated for diagnostic use; rare hypersensitivity reactions can occur. The test and any therapeutic use are directed by clinicians, with results interpreted in the context of the time of day and the patient's overall picture.